The effects of assisted reproduction technologies on metabolic health and disease†

Abstract

The increasing prevalence of metabolic diseases places a substantial burden on human health throughout the world. It is believed that predisposition to metabolic disease starts early in life, a period of great susceptibility to epigenetic reprogramming due to environmental insults. Assisted reproductive technologies (ART), i.e., treatments for infertility, may affect embryo development, resulting in multiple adverse health outcomes in postnatal life. The most frequently observed alteration in ART pregnancies is impaired placental nutrient transfer. Moreover, consequent intrauterine growth restriction and low birth weight followed by catch-up growth can all predict future obesity, insulin resistance, and chronic metabolic diseases. In this review, we have focused on evidence of adverse metabolic alterations associated with ART, which can contribute to the development of chronic adult-onset diseases, such as metabolic syndrome, type 2 diabetes, and cardiovascular disease. Due to high phenotypic plasticity, ART pregnancies can produce both offspring with adverse health outcomes, as well as healthy individuals. We further discuss the sex-specific and age-dependent metabolic alterations reflected in ART offspring, and how the degree of interference of a given ART procedure (from mild to more severe manipulation of the egg) affects the occurrence and degree of offspring alterations. Over the last few years, studies have reported signs of cardiometabolic alterations in ART offspring that are detectable at a young age but that do not appear to constitute a high risk of disease and morbidity per se. These abnormal phenotypes could be early indicators of the development of chronic diseases, including metabolic syndrome, in adulthood. The early detection of metabolic alterations could contribute to preventing the onset of disease in adulthood. Such early interventions may counteract the risk factors and improve the long-term health of the individual.

Epigenetic Effect of Maternal Methyl-Group Donor Intake on Offspring’s Health and Disease

“…Growing evidence suggests that although the majority of children conceived through ART are healthy, they are at increased risk for several perinatal complications, birth defects, alterations in later body composition, metabolic and hormonal changes, and rare imprinting disorders [ 34 , 35 , 36 , 37 ]. Multiple exposures of ART occur at critical windows of development coinciding with global epigenetic reprogramming [ 38 ].…”

Caesarean section and childhood obesity at age 3 years: a large-scale birth cohort study— the Japan Environment and Children’s Study

“…Covariates weight, smoking status, alcohol consumption, and education level are considered to be maternal factors that in uence body habitus of offspring [31][32][33] . Recently, it has been reported that assisted reproduction technology can affect metabolism in offspring 34,35 . Therefore, we included the following maternal covariates in the analysis: age during pregnancy, pre-pregnancy BMI, highest education level, annual household income, smoking status, alcohol consumption, pregnancy complications, obstetric complications, history of physical disease, parity, and use of assisted reproduction technology (i.e., in vitro fertilisation, intracytoplasmic sperm injection, fresh/frozen embryo transfer, and blastocyst transfer).…”

Genome-wide assessment of DNA methylation alterations induced by superovulation, sexual immaturity and in vitro follicle growth in mouse blastocysts

“…Despite the fact that the majority of ART children are born healthy, there is concern about potential long-term consequences related to ovarian stimulation and in vitro culture techniques [ 5 ]. ART conception has been associated with adverse health outcomes such as preterm delivery, low birth weight, being small for gestational age or perinatal mortality [ 6 ]; cardiometabolic alterations [ 7 ]; and imprinting disorders, such as Beckwith–Wiedemann syndrome (BWS), Silver–Russell syndrome (SRS) and Prader–Willi syndrome (PWS) [ 8 ], although the extent to which ART procedures themselves or the underlying infertility of parents contribute is not fully understood. With the extended use of genome-wide approaches, more studies have focused on analyzing the global DNA methylation profile in children conceived by ART.…”